Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers

被引：192

作者：

Nho, Kwangsik ^{[1
,2
]}

Kueider-Paisley, Alexandra ^{[3
]}

MahmoudianDehkordi, Siamak ^{[3
]}

Arnold, Matthias ^{[3
,4
]}

Risacher, Shannon L. ^{[1
,2
]}

Louie, Gregory ^{[3
]}

Blach, Colette ^{[5
]}

Baillie, Rebecca ^{[6
]}

Han, Xianlin ^{[7
]}

Kastenmueller, Gabi ^{[4
,8
]}

Jia, Wei ^{[9
]}

Xie, Guoxiang ^{[9
]}

Ahmad, Shahzad ^{[10
]}

Hankemeier, Thomas ^{[11
]}

van Duijn, Cornelia M. ^{[10
]}

Trojanowski, John Q. ^{[12
]}

Shaw, Leslie M. ^{[12
]}

Weiner, Michael W. ^{[13
]}

Doraiswamy, P. Murali ^{[3
,14
,15
]}

Saykin, Andrew J. ^{[1
,2
]}

Kaddurah-Daouk, Rima ^{[3
,14
,15
]}

Aisen, Paul ^{[17
]}

Weiner, Michael ^{[18
,101
]}

Petersen, Ronald ^{[19
]}

Jack, Clifford R., Jr. ^{[19
]}

Jagust, William ^{[16
,20
]}

Trojanowki, John Q. ^{[21
,46
,103
]}

Toga, Arthur W. ^{[17
,22
]}

Beckett, Laurel ^{[23
]}

Green, Robert C. ^{[24
,100
]}

Morris, John ^{[26
]}

Khachaturian, Zaven ^{[27
]}

Sorensen, Greg ^{[28
]}

Carrillo, Maria ^{[29
]}

Kuller, Lew ^{[30
]}

Raichle, Marc ^{[26
]}

Paul, Steven ^{[31
]}

Davies, Peter ^{[32
]}

Fillit, Howard ^{[33
]}

Hefti, Franz ^{[34
]}

Holtzman, David ^{[26
,35
]}

Mesulam, M. Marcel ^{[35
]}

Potter, William ^{[36
]}

Snyder, Peter ^{[37
]}

Montine, Tom ^{[38
]}

Jimenez, Gustavo ^{[22
]}

Donohue, Michael ^{[22
,39
]}

Gessert, Devon ^{[22
]}

Harless, Kelly ^{[22
]}

Salazar, Jennifer ^{[22
]}

机构：

[1] Indiana Univ Sch Med, Dept Radiol & Imaging Sci, Ctr Computat Biol & Bioinformat, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA

[3] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27708 USA

[4] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany

[5] Duke Univ, Duke Mol Physiol Inst, Durham, NC USA

[6] Rosa & Co LLC, San Carlos, CA USA

[7] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA

[8] German Ctr Diabet Res DZD, Neuherberg, Germany

[9] Univ Hawaii, Canc Ctr, Honolulu, HI 96822 USA

[10] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[11] Leiden Univ, Leiden Acad Ctr Drug Res, Div Analyt Biosci, Leiden, Netherlands

[12] Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA USA

[13] Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Radiol, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94143 USA

[14] Duke Univ, Duke Inst Brain Sci, Durham, NC 27708 USA

[15] Duke Univ, Dept Med, Durham, NC 27708 USA

[16] Univ Calif San Francisco, San Francisco, CA 94143 USA

[17] Univ Southern Calif, Los Angeles, CA USA

[18] UC San Francisco, San Francisco, CA USA

[19] Mayo Clin, Rochester, MN USA

[20] Univ Calif Berkeley, Berkeley, CA USA

[21] Univ Penn, Philadelphia, PA 19104 USA

[22] USC, Los Angeles, CA USA

[23] Univ Calif Davis, Davis, CA USA

[24] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA

[25] Indiana Univ, Bloomington, IN 47405 USA

[26] Washington Univ, St Louis, MO USA

[27] Prevent Alzheimers Dis 2020, Rockville, MD USA

[28] Siemens AG, Washington, DC USA

[29] Alzheimers Assoc, Chicago, IL USA

[30] Univ Pittsburgh, Pittsburgh, PA 15260 USA

[31] Cornell Univ, Ithaca, NY 14853 USA

[32] Yeshiva Univ, Albert Einstein Coll Med, New York, NY 10033 USA

[33] AD Drug Discovery Fdn, New York, NY USA

[34] Acumen Pharmaceut, Livermore, CA USA

[35] Northwestern Univ, Evanston, IL 60208 USA

[36] NIMH, Bethesda, MD 20892 USA

[37] Brown Univ, Providence, RI 02912 USA

[38] Univ Washington, Seattle, WA 98195 USA

[39] Univ Calif San Diego, San Diego, CA USA

[40] Univ London, London, England

[41] UCLA, Sch Med, Los Angeles, CA USA

[42] UCSF, MRI, San Francisco, CA USA

[43] Univ Michigan, Ann Arbor, MI 48109 USA

[44] Univ Utah, Salt Lake City, UT 84112 USA

[45] Banner Alzheimers Inst, Phoenix, AZ USA

[46] UPenn Sch Med, Philadelphia, PA USA

[47] UC Irvine, Irvine, CA USA

[48] NIA, Bethesda, MD 20892 USA

[49] Johns Hopkins Univ, Baltimore, MD 21218 USA

[50] Oregon Hlth & Sci Univ, Portland, OR 97201 USA

来源：

ALZHEIMERS & DEMENTIA | 2019年 / 15卷 / 02期

基金：

加拿大健康研究院; 美国国家卫生研究院;

关键词：

Metabolomics; Bile acid; Alzheimer's disease; Amyloid-beta; CSF biomarkers; Brain glucose metabolism; PET; MRI; Gut-liver-brain axis; ISOLATED RAT HEPATOCYTES; SURFACE-BASED ANALYSIS; GUT-BRAIN AXIS; CEREBROSPINAL-FLUID; CHOLESTEROL-METABOLISM; URSODEOXYCHOLIC ACID; OXIDATIVE STRESS; RANDOM-FIELD; VITAMIN-D; FDG-PET;

D O I：

10.1016/j.jalz.2018.08.012

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammation and amyloid-beta deposition. Method: Serum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD: cerebrospinal fluid (CSF) biomarkers, atrophy (magnetic resonance imaging), and brain glucose metabolism ([F-18]FDG PET). Results: Of 23 BAs and relevant calculated ratios after quality control procedures, three BA signatures were associated with CSFA beta(1-42) ("A") and three with CSF p-tau181 ("T") (corrected P < .05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy ("N"), respectively (corrected P < .05). Discussion: This is the first study to show serum-based BA metabolites are associated with "A/T/N" AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association. (C) 2018 Published by Elsevier Inc. on behalf of the Alzheimer's Association.

引用

页码：232 / 244

页数：13

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